Search Results (198)

Background/Objectives: African swine fever (ASF) causes massive global swine industry losses with no effective vaccine available. This study constructed T7 phages displaying key ASFV proteins to evaluate their potential as an ASF vaccine by assessing viral shedding and immune responses in pigs. Methods: Five ASFV proteins were displayed on T7 phages to form VLPs (ASFV-SC-T7 group), with soluble proteins (ASFV-SC group) and PBS as controls; 9 piglets were immunized, boosted at 28 days, challenged with virulent ASFV, and assessed via ELISA, flow cytometry, and real-time PCR. Results: ASFV-SC-T7 induced more high-titer antibodies and elevated monocytes/CD8⁺ T cells, but all groups developed ASF lesions, with ASFV-SC-T7 having higher lung/mesenteric lymph node viral loads and no survival improvement (only delayed fever). Conclusions: T7 phage-displayed ASFV proteins activate strong immunity, confirming T7 phages as a viable delivery platform, but failed to protect against virulent ASFV, requiring future optimization of antigens and regimens. Full article

Porcine circovirus 2 (PCV2) is still infecting pigs after almost 20 years of massive vaccination all over the world. Vaccines are highly effective at counteracting the clinical signs of systemic disease caused by PCV2 and can significantly reduce the number of subclinically infected pigs. However, current vaccination programs based on one single dose in piglets are insufficient to prevent infection in a proportion of animals. Moreover, systematic vaccination of the herd changes viral epidemiology and, consequently, can cause modifications in infection timing. Such a scenario may prompt intrauterine and piglet early infections, thus facilitating viral circulation even before vaccination takes place. Considering the demonstrated high vaccine efficacy, it would be legitimate to explore the possibility of eliminating PCV2 from swine herds, but only one attempt to eliminate the virus from a herd has been published so far. The present speculative review evaluates the existing scientific literature regarding the feasibility of getting rid of this virus under commercial farm conditions. The use of PCV2 vaccination in all swine populations within a herd and the implementation of regional or national control programs are foreseen as compulsory for the eventual successful elimination of this endemic viral infection. Full article

Background: Since the massive outbreak of foot-and-mouth disease (FMD) in South Korea in 2010–2011, cloven-hoofed livestock have been immunized with serotype O and A vaccines across the country. Other serotypes of FMD vaccines were stockpiled in overseas FMD vaccine factories as antigen banks. Once a manufacturing facility has been established in South Korea, the overseas antigen banks will be replaced by domestic one. Therefore, this study aimed to evaluate the commercial potential of the previously developed SAT2 vaccine candidate (SAT2 ZIM-R). Methods: The optimal condition was determined at various virus concentrations, infection times, and pH levels, resulting in 0.01 MOI for SAT2 ZIM-R for 24 h infection at a pH of 7.5. Results: When the SAT2 ZIM-R virus was produced in flasks from 40 to 1000 mL in fivefold increments, all scales of production yielded > 7.0 µg/mL of antigens. Using a bioreactor, 5.6 µg/mL of antigens was recovered from a 1 L viral culture. The optimal conditions of viral inactivation kinetics were determined to be 1 mM of binary ethyleneimine (BEI) treatment at 26 °C for 24 h, with approximately 91% of the antigen being retained after virus inactivation. When the SAT2 ZIM-R experimental vaccine was administered twice to pigs, the neutralizing antibody titer increased approximately 500-fold after booster immunization. Conclusions: To the best of our knowledge, this is the first study to evaluate the antigen productivity, viral inactivation kinetics, and immunogenicity of the SAT vaccine strain in pigs. In the future, the SAT2 ZIM-R vaccine may be a useful candidate vaccine for a domestic antigen bank. Full article

Background: SARS-CoV-2 was the causing agent of the COVID-19 pandemic, which resulted in millions of deaths worldwide and massive economic losses. Although there are already several vaccines licensed, as novel variants develop, understanding the immune response induced by vaccination and natural infection is key for the development of future vaccines. Methods: In this study, we have used flow cytometry and next-generation sequencing to assess the longitudinal CD8⁺ T-cell response against natural infection and vaccination in convalescent and vaccinated individuals, from early activation to immune memory establishment. Moreover, we have characterized the T-cell receptor clonality and diversity at different stages post-infection and post-vaccination. Results: We have found no significant differences in CD8⁺ T-cell activation during the first three weeks post-infection compared to the first three weeks after first vaccination. Conversely, natural infection resulted in sustained high levels of T-cell activation at four weeks post-infection, a point in which we observed a decline in T-cell activation post-vaccination despite boosting with a second vaccination shot. Moreover, additional vaccination did not result in enhanced T-cell activation. Of note, we have observed variations in the memory subset structure at every stage of disease and vaccination. Overall, both infection and immunization induced a highly diverse T-cell receptor repertoire, which was observed both between study groups and between patients inside a given group. Conclusions: These data contribute to expand our knowledge about the immune response to SARS-CoV-2 infection and vaccination and call for additional strategies to enhance T-cell responses by booster immunization. Full article

Background: In response to the SARS-CoV-2 pandemic, a massive vaccination campaign was launched. Nonetheless, concerns arose regarding some peculiar groups of patients, including those affected by Systemic Lupus Erythematosus (SLE), because of the immune-suppressive drugs routinely administered to patients and the risk of possible disease flares. Since the effects of the third booster vaccination in SLE have been poorly assessed, this study aims to evaluate the immunogenicity and safety of the third BNT162b2 vaccine dose, together with the effects of immunosuppressive drugs. Methods: A monocentric SLE cohort and a cohort of age- and sex-matched healthy controls (HCs) (all vaccinated with three homologous doses) were consecutively enrolled 6 months (T1) after their third vaccine shot. Vaccine immunogenicity was evaluated by analyzing humoral and cellular immune responses at T1 and 12 months (T2). Vaccine safety was evaluated by assessing adverse events related to vaccination (T0) and comparing disease activity among T0, T1, and T2. Effects of immunosuppressive drugs were assessed by stratifying patients according to therapy at vaccination: (1) receiving (IS) or (2) not receiving immunosuppressive drugs (Non-IS). Results: At T1, the humoral responses were comparable between SLE and HC subjects, while the cellular response was significantly higher in HC (p = 0.01). No differences were found at T2 between cohorts. Similarly, both at T1 and T2, the immune responses of IS and Non-IS groups were comparable. Moreover, lupus disease flares were limited and mostly mild, and no life-threatening adverse events were reported. Conclusions: The booster BNT162b2 vaccine is safe and induces an immune response, which is persistent and not affected by ongoing immunosuppressive drugs. Full article

Background: The coronavirus–caused disease (COVID-19), first identified in China in December 2019, has spread worldwide becoming a global pandemic. Although people infected with the SARS-CoV-2 virus presented mainly respiratory and gastrointestinal symptoms, an increase in cardiovascular incidents was observed in several scientific studies. SARS-CoV-2 virus has been shown to disrupt the normal immune response leading to a dysregulation of immune system function and massive production of inflammatory cytokines commonly known as “cytokine storm”. Methods: 57 patients eventually participated in the study, assigned to non–COVID (24 patients) and COVID (33 patients) groups. After signing consent to participate in the study, each patient was given a self–administered questionnaire to fill out prior to specimen collection, anthropometric measurements were taken and venous blood was collected for the following determinations: pro- and anti–inflammatory cytokines using a Bio–Plex 200 system, oxidative stress markers and basic hematological blood parameters. Results: showed statistically significant higher values of IL–1Ra and IL–1β in the COVID-19 group. Of the oxidative stress markers, only MDA levels were higher in the COVID-19 group. Conclusions: the results of our study provide evidence and support the occurrence of elevated levels of IL–1Ra, IL–1β and MDA in the COVID-19 group of patients, which are associated with a worse course and prognosis of COVID-19. A better understanding of the pathophysiology and dysregulation of the immune system associated with the cytokine storm is essential to select patients at risk and develop effective drugs and vaccines. Full article

Introduction: Yellow fever (YF) is a viral hemorrhagic fever transmitted by mosquitoes, characterized by a high mortality due to kidney and liver failure, massive coagulation disorders, and hemorrhages. With no specific treatment, prevention through vaccination and vector control is essential. This study investigates the epidemiology of YF in Brazil from 2011 to 2020, focusing on its trends and distribution across the territory. Methods: This ecological time-series study analyzed confirmed YF cases in Brazil’s 27 federative units between 2011 and 2020. Data were sourced from DATASUS, IBGE, and IPEA. Incidence rates per 100,000 inhabitants were calculated, and various sociodemographic and health indicators were analyzed. Prais–Winsten autoregressive models assessed the trends, while a spatial analysis identified the risk areas using global and local Moran’s I statistics. The data were processed using Stata and GeoDa^® software, version 1.12. Results: YF cases were concentrated in the Amazon and Atlantic Forest biomes. The majority of the cases occurred in males (83.3%), non-white individuals (94.3%), and rural workers. Pará showed an increasing trend in incidence. A higher vaccination coverage correlated with a lower YF incidence, though endemic areas with good vaccination coverage still exhibited high rates. Health and socioeconomic indicators were inversely related to incidence, highlighting disparities in regional development. Conclusion: Effective YF control requires multidisciplinary strategies, including expanded vaccination coverage, intensified vector control, and active surveillance. Research should focus on developing better vaccines, monitoring immunity, and improving the global response coordination. Full article

Background/Objectives: In 2022, the full-scale invasion in Ukraine forced over 6 million Ukrainians, primarily mothers and children, to seek safety outside of the country. This massive influx has posed a significant challenge to the Polish healthcare system, particularly regarding routine vaccination for children. This study aims to examine the vaccination intentions of displaced Ukrainian mothers, their compliance with the Polish National Immunisation Programme (PNIP), and the factors that influence these intentions. Methods: A web-based survey (June–July 2023) was conducted among Ukrainian mothers in Poland. The questionnaire assessed the importance placed on vaccination, knowledge of PNIP, and concerns related to displacement and vaccination. Hierarchical logistic regression identified key determinants. Results: Among 2572 respondents, 64.5% reported that their children had received only some or none of the recommended vaccines. Key barriers included unfamiliarity with PNIP, limited knowledge of vaccines, and concerns about vaccine side effects. Of mothers whose children had not followed PNIP, 41.7% intended to vaccinate, 33.1% refused, and 25.2% were undecided. Regression analysis identified perception of vaccination importance as the strongest predictor. Partial adherence to PNIP doubled vaccination likelihood, while a firm plan to return to Ukraine reduced it 2.4 times. Mistrust in vaccines increased refusal risk tenfold. The final model confirmed mothers’ attitudes towards vaccination and future plans (return to Ukraine) as dominant factors. Conclusions: This study underscores the complex determinants shaping vaccination decisions in conflict-displaced communities. It provides insights for public health strategies to enhance vaccine uptake by reducing access barriers, restoring trust, and strengthening vaccine literacy. Full article

Ostertagia ostertagi, also known as the brown stomach worm, causes significant pathology in the abomasum, resulting in production and nutritional losses in cattle. Alternative control measures, such as vaccination, are urgently needed because of rapidly growing anthelmintic drug resistance. There is a need to understand host responses to the infection, especially immune responses, to advance vaccine discovery and design. Therefore, the present study investigated comprehensive changes in gene transcription in the abomasal mucosa of cattle infected with O. ostertagi at 0, 3–5, 7–9, 10, and 21 days post-infection (dpi) using RNA sequencing (RNA-seq). Compared to uninfected controls, infected animals exhibited significant increases in differentially expressed genes (DEGs) throughout the infection period. Infection induced more upregulated than downregulated genes in the abomasal fundic mucosa (FUN) when compared to the abomasal pyloric mucosa (PYL). The largest transcriptional changes occurred between 7–9 and 10 dpi during the final development of the L4 and their emergence from the gastric glands. Most DEGs are associated with host immunity, cellular reorganization, cell migration, and proliferation. Tuft/epithelial cell response to the infection was atypical, lacking an anticipated increase in key alarmin cytokine genes. Numerous genes associated with T helper (Th) 1, Th2, and Th17 responses and T cell exhaustion were upregulated, suggesting altered immune regulation. The data collectively indicate that O. ostertagi infection elicits massive host responses, particularly immune responses, which are intertwined with the parasite’s disruption of abomasal function, which likely impairs the nutrient utilization of the host. The infection is characterized by the absence of a dominant Th response and displaying a mixed activation of Th1, Th2, and Th17 pathways. Elevated expression of T cell exhaustion genes and lack of increase in epithelial alarmin cytokine genes suggest a downregulation of, or a deficiency in initiating, effective host immunity to the infection. Understanding mechanisms of parasite-mediated immune evasion and their nutritional consequences will facilitate the rational design of protective vaccines against infections of complex nematode parasites. Full article

Persistent oncogenic HPV infection is strongly associated with cervical cancer. Studies have suggested a higher prevalence of HPV in women living with HTLV-1. This study aimed to determine whether HTLV-1 infection is associated with cervicovaginal HPV infection and to characterize HPV types according to oncogenic risk. Vaginal fluid samples were subjected to HPV diagnosis via PCR, and positive samples were subjected to Sanger sequencing and massive sequencing. Papanicolaou smears were examined using light microscopy to identify cell abnormalities. Among the 155 women screened, 79 were HTLV-1-infected and 76 were uninfected. HPV PCR identified 23 positive samples (15/79 vs. 8/76; p = 0.13). Twenty-three HPV types were identified, of which only types 31, 54, and 58 were present in both groups. When the number of HPV58 infections in each group was compared, women with HTLV-1 had a higher prevalence (8/79 versus 1/76; p = 0.03). In total, 61.9% of HTLV-1-infected women had at least one high-risk or probable high-risk HPV type (p = 0.12). Cytopathological findings were not significantly different between the groups. Further research is needed to determine whether HTLV-1 infection affects HPV progression and cervical cancer development and to assess the potential benefits of vaccination for women living with HTLV-1. Full article

Poultry production systems are usually exposed to important infections that could be prevented by vaccination programs. Conventional methods of vaccination such as drinking water; spray, eye, or nose inoculation; and injection are usually given after hatching and have many disadvantages. Therefore, there is a great need for searching of alternative ways for vaccination process. In ovo vaccination technology is now regarded as an alternative approach to post-hatch vaccination in modern poultry operations. This technique is effective, fast, provides uniform vaccine dosing and delivery, is suitable for massive production, and reduces labor costs. Routine in ovo vaccination is applied during the late stage of embryonic development between days 17.5 and 19.25 of egg incubation. The best route of inoculation of the vaccine is in the amniotic fluid or in the embryo’s muscles, without causing any hatchability or chick quality losses. Accordingly, the inoculation site, the age of the embryos and breeders, presence of maternal antibodies, and the sanitation of equipment’s and the environment during the vaccination process affect the efficiency of the in ovo vaccination technique. In ovo vaccination technology is currently applied for vaccination against several economically important viral diseases such as Newcastle, infectious bursal disease, Marek’s disease, infectious laryngotracheitis, infectious bronchitis, avian influenza, and avian metapneumovirus. Moreover, vaccines used for prevention of mycoplasmosis and coccidiosis could be applied in ovo instead of in post-hatching application. It can be concluded that in ovo vaccination is a rapidly growing trend of vaccine technology, and it can replace post-hatching vaccination conventional methods. Full article

Background: Vaccination is the main control measure to prevent Lumpy skin disease (LSD), and Neethling-based homologous vaccines have been shown to be safe and effective against infection with classical clade 1.2 strains. In 2017, recombinant clade 2 LSDV strains originating from a badly produced and insufficiently controlled vaccine were first detected in Russia. A clade 2.5 recombinant strain spread from Russia throughout Southeast Asia and caused a massive epidemic. In this study, the efficacy of three different Neethling strain-based vaccines against the recombinant clade 2.5 LSDV strain was evaluated. Methods: For each vaccine, seven bulls were vaccinated and followed for three weeks to evaluate vaccine safety. Thereafter, vaccinated animals and non-vaccinated controls were challenged with a virulent clade 2.5 strain and followed for three more weeks to evaluate vaccine efficacy. Results: Only limited adverse effects were observed after vaccination, and all vaccinated animals seroconverted and showed an LSDV-specific cellular immune response after vaccination. After the challenge, the vaccinated animals developed almost no clinical signs, and no viremia or nasal excretion was detected. This was in sharp contrast with the non-vaccinated controls, where 8 out of 13 animals developed clinical disease with clear nodules. Most of these animals also had a prolonged period of fever, a clear viremia and excreted virus. Conclusions: Neethling-based LSDV vaccines can thus be considered safe and are effective not only against clade 1.2 LSDV strains, as was proven earlier, but also against a clade 2.5 recombinant strain. Full article

Background/Objectives: The COVID-19 pandemic has revolutionized vaccine production and compelled a massive global vaccination campaign. This study aimed to estimate the positivity and levels of SARS-CoV-2 IgG antibodies acquired due to vaccination and infection in the academic population of a Portuguese university. Methods: Blood samples were collected and analyzed through the ELISA methodology, and statistical analysis was performed. Results: A total of 529 volunteers with at least one dose of the vaccine were enrolled in this study. Individuals without a prior COVID-19 diagnosis were divided into two groups: 350, who received a full vaccination, and 114, who received a full vaccination and a booster dose of the same vaccine (81) and mixed vaccines (33). Regarding the individuals who reported a prior SARS-CoV-2 infection, 31 received a full vaccination, and 34 received only one vaccination dose. Data analysis showed a higher level of IgG against SARS-CoV-2 in individuals who were younger, female, who received the Moderna vaccine, with recent post-vaccine administration, a mixed booster dose, and prior SARS-CoV-2 infection. Conclusions: Assessing vaccination’s effectiveness and group immunity is crucial for pandemic management, particularly in academic environments with high individual mobility, in order to define groups at risk and redirect infection control strategies. Full article

The recent SARS-CoV-2 (COVID-19) pandemic exemplifies how newly emerging and reemerging viruses can quickly overwhelm and cripple global infrastructures. Coupled with synergistic factors such as increasing population densities, the constant and massive mobility of people across geographical areas and substantial changes to ecosystems worldwide, these pathogens pose serious health concerns on a global scale. Vaccines form an indispensable defense, serving to control and mitigate the impact of devastating outbreaks and pandemics. Towards these efforts, we developed a tunable vaccine platform that can be engineered to simultaneously display multiple viral antigens. Here, we describe a second-generation version wherein chimeric proteins derived from SARS-CoV-2 and bacteriophage lambda are engineered and used to decorate phage-like particles with defined surface densities and retention of antigenicity. This streamlines the engineering of particle decoration, thus improving the overall manufacturing potential of the system. In a prime-boost regimen, mice immunized with particles containing as little as 42 copies of the chimeric protein on their surface develop potent neutralizing antibody responses, and immunization protects mice against virulent SARS-CoV-2 challenge. The platform is highly versatile, making it a promising strategy to rapidly develop vaccines against a potentially broad range of infectious diseases. Full article

Brucellosis is a bacterial zoonosis caused by the genus Brucella, which mainly affects domestic animals. In these natural hosts, brucellae display a tropism towards the reproductive organs, such as the placenta, replicating in high numbers and leading to placentitis and abortion, an ability also exerted by the B. melitensis live-attenuated Rev1 strain, the only vaccine available for ovine brucellosis. It is broadly accepted that this tropism is mediated, at least in part, by the presence of certain preferred nutrients in the placenta, particularly erythritol, a polyol that is ultimately incorporated into the Brucella central carbon metabolism via two reactions dependent on transaldolase (Tal) or fructose-bisphosphate aldolase (Fba). In the light of these remarks, we propose that blocking the incorporation of erythritol into the central carbon metabolism of Rev1 by deleting the genes encoding Tal and Fba may impair the ability of the vaccine to proliferate massively in the placenta. Therefore, a Rev1ΔfbaΔtal double mutant was generated and confirmed to be unable to use erythritol. This mutant exhibited a reduced intracellular fitness both in BeWo trophoblasts and THP-1 macrophages. In the murine model, Rev1ΔfbaΔtal provided comparable protection to the Rev1 reference vaccine while inducing fewer adverse reproductive events in pregnant animals. Altogether, these results postulate the Rev1ΔfbaΔtal mutant as a reproductively safer Rev1-derived vaccine candidate to be studied in the natural host. Full article